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Melatonin exhibits partial protective effects against gemcitabine- and cisplatin-induced kidney and reproductive
Shao-Chuan Wang1,2,3, Hsuan-Chih Hsu2, Ya-Chuan Chang1,2
1Department of Urology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
Abstract:
Cisplatin has the potential to cause kidney and reproductive organ injuries, prompting the search for protective agents against cisplatin-induced toxicity. Melatonin, an antioxidant hormone, has shown promise in mitigating oxidative stress in various organs. However, its protective effects on cisplatin-induced kidney and reproductive injuries have not been extensively investigated. The aim of this study was to explore the potential protective effects of melatonin on cisplatin-induced kidney and reproductive injuries when administered in combination with gemcitabine in mice. Male C57BL/6 mice were subjected to a seven-week treatment with gemcitabine plus cisplatin, with or without melatonin intervention. The testis, epididymis, and kidney were assessed through histological analysis and measurement of blood parameters. Treatment with cisplatin led to a significant reduction in testicular weight, histological abnormalities, and alterations in reproductive hormone levels. Melatonin exhibited a slight protective effect on the testis, with higher doses of melatonin yielding better outcomes. However, melatonin did not reverse the effects of cisplatin on the epididymis. Administration of melatonin before and during treatment with cisplatin plus gemcitabine in mice demonstrated a modest protective effect on testicular injuries, while showing limited effects on epididymal injuries. Serum creatinine levels in the group treated with gemcitabine plus cisplatin treatment and high-dose melatonin approached those of the control group, indicating a protective effect on the kidney. These findings underscore the potential of melatonin as a protective agent against cisplatin-induced kidney and reproductive injuries and emphasize the need for further research to optimize its dosage and evaluate its long-term effects.
Insights
Melatonin offers some protection against cisplatin-induced testicular injury and significantly protects the kidneys from damage. Further research is needed to optimize melatonin dosage for reproductive and kidney protection.
Area of Science:
- Toxicology
- Pharmacology
- Reproductive Biology
Background:
- Cisplatin is a chemotherapy drug known to cause kidney and reproductive toxicity.
- Melatonin, an antioxidant, may mitigate cisplatin-induced damage.
- Limited research exists on melatonin's protective effects against cisplatin-induced kidney and reproductive injuries.
Purpose of the Study:
- To investigate the protective potential of melatonin against cisplatin and gemcitabine-induced kidney and reproductive injuries in mice.
- To assess the impact of varying melatonin doses on these toxicities.
Main Methods:
- Male C57BL/6 mice received gemcitabine plus cisplatin for seven weeks, with or without melatonin.
- Histological analysis of testis, epididymis, and kidney were performed.
- Blood parameters and reproductive hormone levels were measured.
Main Results:
- Cisplatin significantly reduced testicular weight and altered reproductive hormones; melatonin showed a dose-dependent protective effect on the testis.
- Melatonin had limited impact on cisplatin-induced epididymal injury.
- High-dose melatonin administration normalized serum creatinine levels, indicating kidney protection.
Conclusions:
- Melatonin demonstrates modest protective effects against cisplatin-induced testicular and significant protective effects against kidney injuries.
- Further studies are warranted to determine optimal melatonin dosage and long-term efficacy.
